Glutathione peroxidase 2 knockdown suppresses gastric cancer progression and metastasis via regulation of kynurenine metabolism.
Oncogene
; 42(24): 1994-2006, 2023 Jun.
Article
em En
| MEDLINE
| ID: mdl-37138031
ABSTRACT
Gastric cancer (GC) is among the most lethal malignancies due to its poor early diagnosis and high metastasis rate, and new therapeutic targets are urgently needed to develop effective anti-GC drugs. Glutathione peroxidase-2 (GPx2) plays various roles in tumor progression and patient survival. Herein, we found that GPx2 was overexpressed and negatively correlated with poor prognosis by using clinical GC samples for validation. GPx2 knockdown suppressed GC proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) in vitro and in vivo. In addition, proteomic analysis revealed that GPx2 expression regulated kynureninase (KYNU)-mediated metabolism. As one of the key proteins involved in tryptophan catabolism, KYNU can degrade the tryptophan metabolite kynurenine (kyn), which is an endogenous ligand for AhR. Next, we revealed that the activation of the reactive oxygen species (ROS)-mediated KYNU-kyn-AhR signaling pathway caused by GPx2 knockdown was involved in GC progression and metastasis. In conclusion, our results showed that GPx2 acted as an oncogene in GC and that GPx2 knockdown suppressed GC progression and metastasis by suppressing the KYNU-kyn-AhR signaling pathway, which was caused by the accumulation of ROS.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
Tipo de estudo:
Screening_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article